Friday 7 January 2022

Basics of immunotherapy

Immunotherapy sounds complicated, but it basically comes down to a simple definition: medical treatments aimed at or using the immune system. Instead of targeting the viruses and other pathogens causing illness, immunotherapy targets the immune system. 

Immunotherapy uses immunomodulators. These are the active ingredients used in the therapy. Examples of immunomodulators  are interleukins, cytokines and specific drugs. They can be administered in several ways:

  • SLIT - sublingual immunotherapy, fancy way of saying that the patient gets the therapy (e.g. drops of liquid) under their tongue. In allergy treatment the liquid would contain the allergen. 
  • SCIT - subcutaneous immunotherapy. The patient gets the therapy injected under their skin.
  • OIT - oral immunotherapy. Patient eats the therapy. For example, a patient eats small portions of the allergen that they're desenziting against.
  • TDIT - Transdermal immunotherapy. The therapy is applied on the skin (fancy term is "epicutaneous application")

Immunotherapies can be divided in two basic categories: activating and suppressing.

Activating therapies are used to elicit a specific response from the immune system. For example, vaccinations are designed to train our immune system to recognize a pathogen and to destroy it. Many side effects of vaccinations are caused by our immune system activating (which is exactly what the vaccine was designed to do!). Activating therapies can also take the patient's own blood cells (for example), enhance them and give them back to the patient. 

Cancer treatments belong to the group of activating therapies. It uses the body's own capabilities to recognize and target cancer cells. The therapy essentially re-trains this natural system to help the body destroy cancer.

Suppressing therapies aim to dim or shut down the immune system. Sounds weird - why would anyone want to do that? For example, many patients develop problems after organ donations because their body recognizes the organ as foreign, and is trying to reject it. This rejection is driven by the immune system. 

Allergy desensitization is also an suppressing immunotherapy. An allergic reaction occurs when the immune system reacts defensively to a harmless substance.  In allergen immunotherapy a patient is given increasingly larger doses of the allergen, which gradually teaches their body to tolerate the allergen better.

Immunotherapeutic testing

A range of veterinary tests and procedures regarding immunotherapy are available. These tests are designated to measure the response of the immune system. Diagnostic immunotherapeutic testing is done prior to treatment in order to determine the correct immunotherapy to be used. For example, blood serum can be tested against different allergens. Once the allergy-inducing substances are recognized, an allergen-specific immunotherapy (ASIT) can be planned.

The names of these tests can sound daunting. In 2013 IDEXX was using a test with a monster of a name: "The canine monoclonal antibody cocktail-based ELISA (macELISA)". Let's break that up, shall we?

Canine = related to canines, mainly dogs. This test is meant for dogs.

Monoclonal = The sample is based on a single cell from the patient. This single cell is cloned. 

Antibody = Antibody, also known as immunoglobulin (Ig), is a protein of the adaptive immune system. That's the part of the immune system that changes and learns. Our immune system uses antibodies to identify antigens (foreign objects such as bacteria and viruses). "Monoclonal antibody"  refers thus to a group of cloned cells which can produce the antibody we're testing for.

cocktail-based = No need for a black dress. This cocktail just means it's a "mix of". In this case it's a mix of antibodies, allowing us to run just one test for several antibodies. 

mac = this is just an acronym of the three previous words, "monoclonal antibody cocktail-based"

 ELISA = enzyme-linked immunosorbent assay. In short, a test that detects antibodies in a sample. Combined with tasty attributes like "sandwich" and "cocktail".


ELISA 

There are several variants of ELISA. In the simplest form (direct ELISA):

  1. A sample is taken and processed per the requirements of the test.
  2. Antigens (viruses, bacteria, other pathogens) are attached to a surface by the manufacturer of the test.
  3. A matching, lab-created antibody is poured over the surface. These antibodies are modified to have a specific active substance called an enzyme.
  4. Antibodies match to antigens in the sample (if any are present). This proves that the suspected antigens were present, but cannot be detected.
  5. Antibodies, which did not get bound, are removed. Now we only have the antibodies bound to antigens left.
  6. A substrate, which reacts with the enzyme, is added. The substrate reacts to the enzyme. If there were any antibodies bound to antigens, they will now show up. 

In short, Elisa takes a sample and shows a specific color if the sought-after antigen was found. The term "cocktail" was already covered: in this case a mix of different antigens is tested in one go. In the "sandwich" ELISA the test begins with specific antibodies, which only respond to specific antigens. The antigens are added, and eventually a another layer of antibodies is added. The term "sandwich" refers to the antigens from the sample getting stuck between two layers of antibodies.  The second layer of antibodies binds to a variety of antigenes. It's less picky than the first one.  Instead of creating specific antibodies with their own enzymes, a generic antibody-enzyme -pair is used.  


More information

https://en.wikipedia.org/wiki/Immunotherapy